Xu Hui, Cao Yu, Ruan Jianqiao, Wang Fei, He Yuhong, Yang Lina, Yu Tian, Du Fang, Zhang Ningmei, Cao Xiangmei
Department of Pathology, General Hospital of Ningxia Medical University, 804 Shengli South Street, Yinchuan, 750004, Ningxia Hui Autonomous Region, P.R. China.
Department of Pathology, The First People's Hospital of Yinchuan, Yinchuan, 750001, Ningxia, China.
J Neurooncol. 2024 Oct;170(1):161-171. doi: 10.1007/s11060-024-04789-x. Epub 2024 Aug 8.
This study investigated the effect of an isocitrate dehydrogenase 1 (IDH1) mutation (mutIDH1) on the invasion and angiogenesis of human glioma cells.
Doxycycline was used to induce the expression of mutIDH1 in glioma cells. Transwell and wound healing assays were conducted to assess glioma cell migration and invasion. Western blotting and cell immunofluorescence were used to measure the expression levels of various proteins. The influence of bone morphogenetic protein 2 (BMP2) on invasion, angiogenesis-related factors, BMP2-related receptor expression, and changes in Smad signaling pathway-related proteins were evaluated after treatment with BMP2. Differential gene expression and reference transcription analysis were performed.
Successful infection with recombinant lentivirus expressing mutIDH1 was demonstrated. The IDH1 mutation promoted glioma cell migration and invasion while positively regulating the expression of vascularization-related factors and BMP2-related receptors. BMP2 exhibited a positive regulatory effect on the migration, invasion, and angiogenesis of mutIDH1-glioma cells, possibly mediated by BMP2-induced alterations in Smad signaling pathway-related factors.After BMP2 treatment, the differential genes of MutIDH1-glioma cells are closely related to the regulation of cell migration and cell adhesion, especially the regulation of Smad-related proteins. KEGG analysis confirmed that it was related to BMP signaling pathway and TGF-β signaling pathway and cell adhesion. Enrichment analysis of gene ontology and genome encyclopedia further confirmed the correlation of these pathways.
Mutation of isocitrate dehydrogenase 1 promotes the migration, invasion, and angiogenesis of glioma cells, through its effects on the BMP2-driven Smad signaling pathway. In addition, BMP2 altered the transcriptional patterns of mutIDH1 glioma cells, enriching different gene loci in pathways associated with invasion, migration, and angiogenesis.
本研究调查了异柠檬酸脱氢酶1（IDH1）突变（mutIDH1）对人胶质瘤细胞侵袭和血管生成的影响。
使用强力霉素诱导胶质瘤细胞中mutIDH1的表达。进行Transwell和伤口愈合试验以评估胶质瘤细胞的迁移和侵袭。采用蛋白质免疫印迹法和细胞免疫荧光法检测各种蛋白质的表达水平。用骨形态发生蛋白2（BMP2）处理后，评估BMP2对侵袭、血管生成相关因子、BMP2相关受体表达以及Smad信号通路相关蛋白变化的影响。进行差异基因表达和参考转录分析。
证实成功感染表达mutIDH1的重组慢病毒。IDH1突变促进胶质瘤细胞迁移和侵袭，同时正向调节血管生成相关因子和BMP2相关受体的表达。BMP2对mutIDH1胶质瘤细胞的迁移、侵袭和血管生成具有正向调节作用，可能由BMP2诱导的Smad信号通路相关因子改变介导。BMP2处理后，MutIDH1胶质瘤细胞的差异基因与细胞迁移和细胞黏附的调节密切相关，尤其是Smad相关蛋白的调节。KEGG分析证实其与BMP信号通路、TGF-β信号通路和细胞黏附有关。基因本体论和基因组百科全书的富集分析进一步证实了这些通路的相关性。
异柠檬酸脱氢酶1突变通过其对BMP2驱动的Smad信号通路的影响，促进胶质瘤细胞的迁移、侵袭和血管生成。此外，BMP2改变了mutIDH1胶质瘤细胞的转录模式，使与侵袭、迁移和血管生成相关的通路中的不同基因位点富集。
